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Updated: May 22, 2026

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Tumour necrosis factor-alpha enhances intraepithelial lymphocyte proliferation and migration
1Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
Background:
Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine found in abundance in diseased intestine.
Aims:
The T cell production of TNF-alpha and the impact of this cytokine on intestinal T cell proliferation, migration, and cytotoxicity were studied.
Methods:
Intestinal lymphocytes from normal jejunum were used. TNF-alpha production in culture supernates was measured by enzyme linked immunosorbent assay (ELISA). Lymphocyte proliferation was measured using 3H thymidine uptake; migration, using transwell chambers; and cytotoxicity of HT-29 colon cancer cells, using the chromium-51 release assay.
Results:
TNF-alpha was produced mainly by the CD8+ T cells in the intraepithelial lymphocytes (IEL) and the CD4+ T cells in the lamina propria lymphocytes in response to CD2 stimulation: 478 (94) and 782 (136) pg/ml, respectively. TNF-alpha (1 ng/ml or greater) augmented proliferation of IEL in response to interleukin 2 (IL-2), IL-7, or antibody to CD3 due to increased activation that did not involve IL-2 production or receptor generation. Conversely, antibody to TNF-alpha reduced IEL proliferation in response to IL-2 or IL-7. TNF-alpha also induced calcium mobilisation and chemokinesis (by 2.8 (0.5) fold over spontaneous migration). TNF-alpha had no effect on lymphokine activated killer cell activity.
Conclusions:
TNF-alpha increases the proliferation and migration of IEL, which may expand their number in the epithelium.
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